Cell packaging filter element and cell therapy delivery system

Abstract

The utility model relates to the technical field of cell therapy equipment, and discloses a cell packaging filter element and a cell therapy delivery system.The cell packaging filter element comprises a collecting container and an inflow connector used for allowing liquid to flow into the collecting container, the outflow connector is used for allowing liquid to flow out of the collecting container; the packaging part is arranged in the collecting container and detachably connected with the collecting container, the packaging part comprises a support membrane plate, a retention cavity for retaining cells is formed in the support membrane plate, a porous membrane used for packaging the retention cavity and allowing cell products to permeate out is arranged on the support membrane plate, and the porous membrane is arranged on the support membrane plate. The porous membrane covers the surface of the bracket membrane plate and can be in contact with liquid; the cell therapy delivery system disclosed by the utility model comprises the cell packaging filter element. According to the utility model, the technical effects that the bioactive substances are collected in vitro, and the stent diaphragm plate can be repeatedly used to reduce the cost are achieved.

Description

Technical Field

[0001] The utility model belongs to the technical field of cell therapy equipment, and particularly relates to a cell encapsulation filter element and a cell therapy delivery system. Background Art

[0002] Cell therapy refers to a method of treating diseases by using bioactive molecules of natural or engineered cells, or directly using cells as functional units. Based on the principles of cell biology and immunology, cell therapy regulates cell functions or utilizes their characteristics to achieve the effect of treating diseases. Currently, cell therapy has been widely used in the treatment of various diseases, including research on endocrine disorders, cardiovascular diseases, cancers, and neurological diseases.

[0003] To reduce the possibility of severe immune rejection reactions in the human body when directly injecting cells for treatment using cells as functional units, and to solve the problem that the retention time of bioactive molecules produced by injected cells in the body and at the lesion site is relatively short, cell delivery therapy can use implantable devices to deliver cells or bioactive molecules with the help of implantable devices to meet the nutritional requirements of cells and protect newly introduced cells from attack by the human immune system. Among them, implantable devices include membrane-controlled release devices. Existing membrane-controlled release devices mainly include two layers of porous membranes. A cavity for storing cells is formed between the two layers of porous membranes. The two layers of porous membranes encapsulate the cells. After the membrane-controlled release device is implanted into the patient's body, the bioactive substances produced by the cells can penetrate through the porous membranes to play a role, achieving the effect of treating diseases. The membrane-controlled release device has good biocompatibility, can maintain the integrity of the cell functional structure, and reduce the occurrence of immune reactions.

[0004] However, the membrane-controlled release device is a disposable device that needs to be implanted into the patient's body, with a relatively high cost and inconvenience in the use process. Summary of the Utility Model

[0005] To solve the deficiencies of the above-mentioned prior art, the utility model provides a cell encapsulation filter element and a cell therapy delivery system. The cell encapsulation filter element of the utility model can collect and deliver the bioactive molecules metabolically secreted by cells to the patient's body in vitro. The support membrane plate in the encapsulation part can be detachably cleaned, sterilized, and reused, which is beneficial to reducing the use cost and improving the convenience of the membrane-controlled release device in the use process. The cell encapsulation filter element of the utility model is used in cell therapy, can obtain the bioactive substances produced by cell secretion and metabolism in vitro, including but not limited to insulin, monoclonal antibodies, exosomes, etc., can protect cells from attack by the human immune system, and maintain a relatively long survival period of cells.

[0006] The technical effects to be achieved by the utility model are realized through the following technical aspects:

[0007] In a first aspect, the present utility model provides a cell encapsulation filter element, comprising a collection container provided with an inflow joint for allowing liquid to flow into the collection container and an outflow joint for allowing liquid to flow out of the collection container; and an encapsulation member detachably connected to the collection container within the collection container. The encapsulation member includes a support membrane plate having a retention cavity for retaining cells. A porous membrane for encapsulating the retention cavity and allowing cell products to pass through is provided on the support membrane plate. The porous membrane covers the surface of the support membrane plate and can contact the liquid.

[0008] In some implementation manners, branches for dispersing cells in the retention cavity are provided on the inner wall of the retention cavity of the support membrane plate.

[0009] In some implementation manners, there are a plurality of the branches, and the plurality of branches are spaced along the inner wall of the retention cavity. Among them, two relatively arranged branches are staggered.

[0010] In some implementation manners, the branches extend into the retention cavity and bend in a direction opposite to the direction of gravity, forming a plurality of dispersion chambers separated by the branches.

[0011] In some implementation manners, perfusion holes for pouring cells into the retention cavity are provided on the support membrane plate, and a sealing plug is provided on the support membrane plate at the perfusion holes.

[0012] In some implementation manners, a split groove box adapted to the inner wall of the collection container is provided in the collection container. Fixing holes are provided on the split groove box, and the encapsulation member is placed in the split groove box through the fixing holes; the collection container includes a housing, and flow-through holes communicating with the housing are provided on the split groove box.

[0013] In some implementation manners, there are a plurality of the fixing holes, and the plurality of fixing holes are spaced. At least a part of the encapsulation member extends out of the split groove box in the direction of the inflow joint.

[0014] In some implementation manners, the outflow joint is provided at the top of the collection container.

[0015] In a second aspect, the present utility model provides a cell therapy delivery system, comprising the above-mentioned cell encapsulation filter element.

[0016] In some implementation manners, it further includes a membrane oxygenator and a liquid delivery device for driving the flow of liquid. Among them, the liquid delivery device is connected to the cell encapsulation filter element to drive the flow of liquid, and the membrane oxygenator is connected to the inflow joint.

[0017] In summary, the present utility model has at least the following advantages:

[0018] 1. The cell encapsulation filter element provided by the present utility model fills cells, microcarriers adhered with cells or culture media loaded with cells into the retention cavity through perfusion holes, seals the perfusion holes with a sealing plug, encapsulates the cells in the encapsulation member, and then shakes the encapsulation member to uniformly disperse the cells in the retention cavity. When the encapsulation member is placed in the collection container, the collection container is filled with liquid through the inflow joint, the liquid flows through the encapsulation member, and the bioactive substances produced by the cells penetrate through the porous membrane and permeate into the liquid. The liquid with the attached bioactive substances flows out through the outflow joint, and the bioactive substances are collected in vitro, which is beneficial to protecting the cells to reduce the attack of the immune system, maintaining the long-term survival of the cells, and the in vitro filtration is beneficial to observing the cell state in a timely manner.

[0019] When it is necessary to replace the encapsulation member due to depletion of the culture medium nutrients, etc., the encapsulation member can be removed from the collection container, the porous membrane can be scratched to pour out the culture medium or microcarriers filled in the retention cavity, and the support membrane plate can be reused after cleaning and sterilization treatment to encapsulate the porous membrane again, for multiple cycles of use, reducing the production and use costs of the existing membrane-controlled release devices. The cell encapsulation filter element of the present utility model has a simple structure and is convenient to use.

[0020] 2. The cell therapy delivery system provided by the present utility model has liquid flowing into the collection container, and the liquid loaded with the bioactive substances produced by the cells flows out of the collection container to collect the bioactive substances, which is beneficial to the reinfusion of the bioactive substances into the patient's body to achieve the purpose of treating diseases. Description of the Drawings

[0021] Figure 1 It is a schematic diagram of the overall structure of the cell encapsulation filter element in a specific embodiment of the present utility model.

[0022] Figure 2 It is an exploded view of the cell encapsulation filter element in a specific embodiment of the present utility model.

[0023] Figure 3 It is an exploded view of the encapsulation member in a specific embodiment of the present utility model.

[0024] Figure 4 It is a schematic diagram of the structure of the support membrane plate in a specific embodiment of the present utility model.

[0025] Figure 5 It is an application schematic diagram of the cell encapsulation filter element in a specific embodiment of the present utility model.

[0026] Figure 6 It is a schematic diagram of the overall structure of the slotting box and the encapsulation member in a specific embodiment of the present utility model.

[0027] Figure 7 It is a schematic diagram of the overall structure of the cell therapy delivery system in a specific embodiment of the present utility model.

[0028] Figure 8 Schematic diagram of the change in IL-6 levels in the model group and the experimental group in the sepsis animal model of Embodiment 4 of the present utility model.

[0029] Figure 9 Schematic diagram of the change in serum creatinine levels in the model group and the experimental group in the sepsis animal model of Embodiment 4 of the present utility model.

[0030] Figure 10 Schematic diagram of the change in urea levels in the model group and the experimental group in the sepsis animal model of Embodiment 4 of the present utility model.

[0031] Figure 11 Schematic diagram of the change in aspartate aminotransferase levels in the model group and the experimental group in the sepsis animal model of Embodiment 4 of the present utility model.

[0032] Figure 12 Schematic diagram of the change in alanine aminotransferase levels in the model group and the experimental group in the sepsis animal model of Embodiment 4 of the present utility model.

[0033] Markings in the figure:

[0034] 1. Collection container; 11. End cap; 111. Outflow joint; 12. Housing; 121. Inflow joint;

[0035] 2. Encapsulation member; 21. Support membrane plate; 211. Retention cavity; 2111. Branch; 2112. Dispersion chamber; 2113. Connection section; 212. Perfusion hole; 213. Sealing plug; 22. Porous membrane;

[0036] 3. Sub-slot box; 31. Fixing hole; 32. Flow-through hole;

[0037] 41. Inflow tube; 42. Outflow tube; 43. Vascular interface;

[0038] 5. Membrane oxygenator; 51. Liquid delivery device;

[0039] 6. Receiver. Detailed implementation manners

[0040] To make the purpose, technical solutions, and advantages of the embodiments of the present utility model clearer, the technical solutions in the embodiments of the present utility model will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present utility model. The described embodiments are part of the embodiments of the present utility model, rather than all of the embodiments.

[0041] Accordingly, the following detailed description of the embodiments of the present invention provided in the drawings is not intended to limit the scope of the claimed present invention, but merely represents selected embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present invention without creative efforts fall within the scope of protection of the present invention.

[0042] Example 1:

[0043] Please refer to the attached Figures 1-5 , the cell encapsulation filter element of the present invention includes a collection container 1, and an encapsulation member 2 for encapsulating cells is arranged in the collection container 1, which can be applied to cell therapy to provide a survival environment for cells to collect bioactive substances secreted and metabolized by cells in vitro.

[0044] Among them, please refer to the attached Figure 1 and Figure 2 , an inflow joint 121 is arranged on the collection container 1, and the inflow joint 121 is communicated with the collection container 1 for allowing liquid to flow into the collection container 1. An outflow joint 111 is arranged on the collection container 1, and the outflow joint 111 is communicated with the collection container 1 for allowing liquid and bioactive substances to flow out of the collection container 1.

[0045] Specifically, the inflow joint 121 and the outflow joint 111 are arranged on the collection container 1 in a direction away from each other, aiming to allow bioactive molecules secreted by cells to diffuse or permeate out of the encapsulation member 2 and then be fully carried away by the flowing liquid, so as to ensure that the bioactive substances fully diffuse or permeate into the liquid. The liquid can be dialysis fluid or blood and other liquids. Among them, using blood can be transfused back into the patient's body to achieve the purpose of treating diseases.

[0046] Please refer to the attached Figure 3 and Figure 4 , the encapsulation member 2 is arranged in the collection container 1 and is detachably connected to the collection container 1. The encapsulation member 2 includes a support membrane plate 21. Specifically, the support membrane plate 21 is a rectangular plate, and a retention cavity 211 for retaining cells is formed through the support membrane plate 21. The retention cavity 211 is specifically a square cavity. In a preferred embodiment, a plurality of retention cavities 211 are provided. For example, in a specific embodiment, two retention cavities 211 can be provided, and the two retention cavities 211 are symmetrically distributed to disperse the cells and ensure that the cells are evenly distributed in the retention cavity 211.

[0047] A porous membrane 22 is provided on the support membrane plate 21. In some specific embodiments shown, the porous membrane 22 covers both side surfaces of the support membrane plate 21 along the length direction to enclose the retention cavity 211. The porous membrane 22 can be in direct contact with the liquid, so that the bioactive substances produced by the cells can permeate out from the porous membrane 22. After the bioactive substances diffuse or permeate out from the porous membrane 22, they flow out of the collection container 1 along with the liquid. In a preferred embodiment, the porous membrane 22 can be attached to the surface of the support membrane plate 21, and the support membrane plate 21 is hermetically connected to the porous membrane 22. At the same time, the porous membrane 22 is preferably but not limited to using one of PTF E membrane, PES membrane, PPSU membrane or PC membrane. The pore size of the porous membrane 22 is preferably but not limited to 100 nm to 1 μm.

[0048] It can be understood that this is not a specific limitation on the selection of the porous membrane 22. Those skilled in the relevant art can select a porous membrane 22 with appropriate pores and materials according to the shape, size and characteristics of molecules such as bioactive substances, so as to achieve the selective permeation of the bioactive substances by the encapsulation member 2. The bioactive substances can include but are not limited to insulin, monoclonal antibodies and exosomes, etc. The porous membrane 22 covers the surface of the support membrane plate 21 to enclose the retention cavity 211, and the cells are encapsulated in the retention cavity 211.

[0049] Before use, first seal the bottom of the support membrane plate 21, that is, one side of the porous membrane 22 encloses the retention cavity 211 of the support membrane plate 21. Pour the culture medium containing cells or microcarriers carrying cells into the retention cavity 211, and then perform the sealing operation of the support membrane plate 21, that is, the porous membrane 22 encloses the other side of the retention cavity 211. Shake the cells evenly, and the cells are dispersed in the retention cavity 211. The microcarriers or the culture medium provide the necessary nutrients for the cells, and the cells survive for a long time. The encapsulation member 2 is placed in the collection container 1 and is detachably connected to the collection container 1, and the cell encapsulation filter element is completed for assembly. When the liquid is introduced into the collection container 1 through the inflow joint 121, the bioactive substances produced by the cells permeate or diffuse through the porous membrane 22 into the liquid and flow out of the collection container 1 through the outflow joint 111 along with the liquid, and the bioactive substances are collected in vitro.

[0050] Please refer to the attached Figure 5 , when the cell encapsulation filter element is applied to a perfusion device to separately collect the products secreted by the cells, the collection container 1 inputs the dialysis fluid through the inflow joint 121 and is connected to the receiver 6 through the outflow joint 111. The bioactive substances produced by the cells permeate through the porous membrane 22 of the cell encapsulation filter element into the dialysis fluid and are brought to the receiver 6 by the dialysis fluid to complete the collection.

[0051] When the nutrients in the culture medium or microcarriers are exhausted, the encapsulation member 2 can be taken out from the collection container 1, the porous membrane 22 can be cut with a knife, and then the microcarriers or culture medium can be poured out. The support membrane template 21 is cleaned and sterilized. After cleaning, the support membrane template 21 encapsulates the porous membrane 22 again, and can be recycled multiple times, effectively reducing the cost of using the cell encapsulation filter element, replacing the existing disposable membrane-controlled release device, and improving the convenience of use.

[0052] Example 2:

[0053] The difference between this example and the above example is that in this example, further structural optimization is performed on the cell encapsulation filter element of the present invention. Please refer to Figure 2 and Figure 3 .

[0054] The collection container 1 includes an end cap 11 and a housing 12. In some specific embodiments shown, the housing 12 is a circular tube, and the end cap 11 is sleeved at the pipe orifice of the housing 12 and is detachably connected to the housing 12. In a preferred embodiment, the inner wall of the end cap 11 is threadedly connected to the outer wall of the housing 12.

[0055] In some other specific embodiments, the end cap 11 and the housing 12 can be snap-fitted. The end cap 11 is sleeved on the housing 12 to achieve snap-fitting, and the operation is simple. A sealing ring is provided in the end cap 11, and the end cap 11 is hermetically connected to the housing 12 through the sealing ring. The end cap 11 and the housing 12 are detachably connected, and the collection container 1 can be quickly disassembled and assembled to facilitate the replacement of the encapsulation member 2. Among them, in some specific embodiments shown, the inflow joint 121 can be provided on the housing 12, and the outflow joint 111 can be provided on the end cap 11.

[0056] In a preferred embodiment, the outflow joint 111 can be provided at the top of the collection container 1. When the collection container 1 is placed upright, the outflow joint 111 is located at the top of the collection container 1, while the inflow joint 121 is located at the bottom of the collection container 1. At this time, it is beneficial for the liquid to overcome gravity work when flowing through the collection container 1, fully contact with the porous membrane 22, and further enable the bioactive substance to fully diffuse or penetrate into the liquid.

[0057] In a preferred embodiment, a perfusion hole 212 for pouring cells into the retention cavity 211 is provided on the support membrane template 21. The perfusion hole 212 is communicated with the retention cavity 211. Specifically, the perfusion hole 212 is a circular through hole at one end of the support membrane template 21 along the length direction. A sealing plug 213 is provided in the perfusion hole 212 of the support membrane template 21. The sealing plug 213 blocks the perfusion hole 212 to reduce the possibility of cell overflow. The sealing plug 213 is preferably but not limited to a silica gel column. The porous membrane 22 and the sealing plug 213 cooperate to form a closed retention cavity 211, and the cells are encapsulated in the retention cavity 211.

[0058] Before use, the culture medium containing cells or microcarriers carrying cells is poured into the retention chamber 211 through the perfusion hole 212. The perfusion hole 212 is sealed with the sealing plug 213, and then the cells are shaken evenly. The cells are dispersed in the retention chamber 211. The microcarriers or the culture medium provide the necessary nutrients for the cells, and the cells can survive for a long time. The encapsulation member 2 is placed into the housing 12, and the end cap 11 is threadedly connected to the housing 12. The cell encapsulation filter element is assembled, and the disassembly and assembly of the cell encapsulation filter element are convenient, which is beneficial to the recycling of the encapsulation member 2.

[0059] Example 3:

[0060] The difference between this example and the above examples is that in this example, further structural optimization is made to the encapsulation member 2 of the present invention. Please refer to Figure 3 、 4 and 6.

[0061] Please refer to Figure 3 and Figure 4 , in the support membrane plate 21 of this example, branches 2111 for dispersing the cells in the retention chamber 211 are arranged on the inner wall of the retention chamber 211. The support membrane plate 21 disperses the cells evenly through the branches 2111, which can reduce the possibility of cell aggregation and blockage in the retention chamber 211. In a preferred embodiment, several branches 2111 are provided. In some specific embodiments shown, ten branches 2111 can be provided in a single retention chamber 211. The several branches 2111 are spaced along the inner wall of the retention chamber 211. Among them, two relatively arranged branches 2111 are distributed alternately. In the same retention chamber 211, branches 2111 extend from the inner walls on the opposite sides of the retention chamber 211 at intervals. The branches 2111 on both sides do not face each other, and the branches 2111 are spaced from the retention chamber 211 so that the retention chamber 211 is a zigzag linear cavity, which is beneficial to dispersing the cells in the retention chamber 211.

[0062] In a preferred embodiment, the branches 2111 extend into the retention chamber 211 and bend in a direction opposite to the direction of gravity. When the encapsulation member 2 is placed vertically, the cells or the microcarriers carrying the cells sink to the bottom under the action of gravity, and the branches 2111 can disperse the cells or the microcarriers carrying the cells. The branches 2111 divide the space of the retention chamber 211 into multiple dispersion chambers 2112, which helps the uniform distribution of the cells or the microcarriers carrying the cells in the liquid flow phase of the porous membrane 22, improves the mass exchange efficiency in the encapsulation member 2; the uniform distribution of the cells or the cell microcarriers helps to extend the cell survival rate and improve the cell proliferation rate; it helps to discharge the bubbles in the stacked porous membranes 22.

[0063] Specifically, the branch 2111 can be bent to form an L shape to further disperse the cells retained in the retention cavity 211. The arrangement of the branch 2111 can increase the cell attachment area, which is beneficial for the retention cavity 211 to accommodate more cells and provide more adhesion points for the cells. Further, a connecting section 2113 is provided between the bent portion of the branch 2111 and the inner wall of the retention cavity 211. The arrangement of the connecting section 2113 can enhance the structural strength of the scaffold template 21 to extend the service life of the scaffold template 21.

[0064] Please refer to Figure 6 , in a preferred embodiment, a slotting box 3 is provided in the housing 12. Specifically, the slotting box 3 is a hollow cylinder. In some specific embodiments shown, the slotting box 3 is adapted to the housing 12, that is, the outer wall of the slotting box 3 fits against the inner wall of the housing 12, and the slotting box 3 is embedded in the housing 12. Fixing holes 31 are formed in the slotting box 3. In a preferred embodiment, a plurality of fixing holes 31 are provided. The plurality of fixing holes 31 are respectively distributed at both ends of the slotting box 3 along the length direction, and the plurality of fixing holes 31 at both ends are arranged in one-to-one correspondence, which is beneficial for the placement and fixation of the encapsulation member 2. Among them, the plurality of fixing holes 31 at one end of the slotting box 3 along the axial direction are distributed along the diameter direction of the slotting box 3. In some specific embodiments shown, nine fixing holes 31 are provided at one end of the slotting box 3 along the axial direction. The fixing holes 31 are specifically rectangular through holes, and the lengths of the plurality of fixing holes 31 increase or decrease along the diameter direction of the slotting box 3 so that the sizes of the fixing holes 31 are adapted to the cross-sectional size of the slotting box 3.

[0065] In a preferred embodiment, the encapsulation member 2 is adapted to the fixing hole 31. The encapsulation member 2 is placed in the fixing hole 31. The slotting box 3 plays a role in supporting and fixing the encapsulation member 2 and spaces multiple encapsulation members 2. The arrangement of the slotting box 3 can effectively utilize the space in the housing 12. At this time, there is a gap between the encapsulation member 2 and the inner wall of the fixing hole 31 for the liquid to pass through the fixing hole 31, and the liquid flows through the slotting box 3. The encapsulation member 2 and the slotting box 3 are detachably connected, which is beneficial to improve the convenience of disassembly and assembly, so as to facilitate the recycling of the scaffold template 21 and the slotting box 3.

[0066] In a preferred embodiment, when the encapsulation member 2 is placed in the slotting box 3, one end of the encapsulation member 2 close to the outflow joint 111 extends at least partially from the slotting box 3 towards the outflow joint 111, which is beneficial for the porous membrane 22 to be in full contact with the liquid. Of course, the encapsulation member 2 may not extend out of the slotting box 3, and the porous membrane 22 only contacts the liquid through the fixing hole 31, which can be determined according to the actual situation.

[0067] The outer wall of the slot-dividing box 3 is penetrated with flow holes 32. The slot-dividing box 3 communicates with the housing 12 at the positions of the flow holes 32. In a preferred embodiment, a plurality of flow holes 32 are provided, and the plurality of flow holes 32 are distributed at intervals along the annular outer wall of the slot-dividing box 3. The arrangement of the flow holes 32 is conducive to the circulation of liquid in the housing 12 and improves the mass transfer efficiency at the porous membrane 22.

[0068] The encapsulation member 2 is snapped into the fixing hole 31. The slot-dividing box 3 fixes and supports the encapsulation member 2. After the slot-dividing box 3 is placed in the housing 12, the housing 12 and the end cover 11 are threadedly connected, and the cell encapsulation filter element is assembled. The operation is simple, which is conducive to improving the convenience of use. A reasonable cell retention space is formed between the support membrane plate 21 and the porous membrane 22. By shaking the encapsulation member 2, the cells can be evenly dispersed in each dispersion chamber 2112. Then, the encapsulation member 2 is placed in the slot-dividing box 3. The slot-dividing box 3 supports a plurality of encapsulation members 2 at the same time, which is conducive to making full use of the space in the housing 12. The support membrane plate 21 occupies a small volume and can retain more cells, improving the permeation efficiency of the cell encapsulation filter element and ensuring the treatment effect of cell therapy.

[0069] Embodiment 4:

[0070] On the basis of the above embodiments, this embodiment provides a cell therapy system. Please refer to Figures 7-12 .

[0071] Please refer to Figure 7 , a cell therapy delivery system, including the above cell encapsulation filter element. The cell encapsulation filter element is connected with a membrane oxygenator 5 and a liquid delivery device 51. Preferably, an inflow pipe 41 is connected to the input end of the membrane oxygenator 5, and an outflow pipe 42 is connected to the output end of the outflow joint 111. Specifically, both the inflow pipe 41 and the outflow pipe 42 are preferably but not limited to being made of silica gel tubes. The inflow pipe 41 is connected to the input end of the membrane oxygenator 5, the output end of the membrane oxygenator 5 is connected to the liquid delivery device 51. The liquid delivery device 51 is preferably but not limited to being a peristaltic pump. The liquid delivery device 51 pumps the liquid. The output end of the liquid delivery device 51 is connected to the inflow joint 121 of the cell encapsulation filter element, and the outflow joint 111 of the cell encapsulation filter element is connected to the outflow pipe 42. Specifically, blood vessel interfaces 42 are connected to one end of the inflow pipe 41 far from the membrane oxygenator 5 and one end of the outflow pipe 42 far from the cell encapsulation filter element.

[0072] In a preferred embodiment, a support shell is sleeved outside the cell encapsulation filter element. The cell encapsulation filter element can be placed in the support shell. The support shell can support and protect the cell encapsulation filter element, and the cell encapsulation filter element can be vertically placed on the operation table.

[0073] When the cell therapy delivery system is working, the patient's blood flows into the membrane oxygenator 5, and the membrane oxygenator 5 is separated by a porous membrane to form a blood passage and a gas passage. Specifically, the membrane in the membrane oxygenator 5 can be any of a non-porous type and a porous type. The method of using a non-porous membrane or a porous membrane to separate the blood passage and the gas passage by the membrane oxygenator 5 is known to those skilled in the art and is achievable, so it will not be described in detail in this embodiment. When the patient's blood flows through the membrane oxygenator, the blood passage and the gas passage exchange CO2 and O2 between the gas and liquid. Blood oxygen is provided to the patient and the cells in the cell encapsulation filter element. After passing through the membrane oxygenator 5, the patient's blood flows into the cell encapsulation filter element. The bioactive molecules produced by the cells in the encapsulation 2 of the cell encapsulation filter element pass through the porous membrane 22 into the patient's blood and finally flow back into the patient's body. The bioactive molecules play a role in the patient's body, achieving the purpose of disease treatment.

[0074] Cell encapsulation filters are used in cell therapy to obtain active molecules produced by cell secretion and metabolism in vitro, including but not limited to insulin, monoclonal antibodies and exosomes, which can protect cells from attacks by the human immune system and maintain a longer cell survival period.

[0075] Test example

[0076] Specifically, the cell therapy delivery system is used to treat an animal model of sepsis, wherein female Bama pigs weighing 30 to 40 kg can be used for animal modeling. The Bama pigs are divided into a model group and a test group, with one pig in each group.

[0077] Autologous feces were collected from the model and experimental groups. The feces were mixed with 200 mL of sterile saline at a concentration of 0.5 g / kg of animal body weight and incubated at 25-30°C for 15 hours to obtain a fecal suspension. In both the model and experimental groups, 200 mL of the fecal suspension was injected into the left lower abdomen of Bama pigs. A central venous catheter was placed in the carotid artery as a sampling point. Animal models were established in both groups.

[0078] 1×10 human umbilical cord mesenchymal stem cells (MSCs) were injected from perfusion well 212. 8 and perfused with DMEM medium containing 10% fetal bovine serum and 1×10 urinary tract-derived cells (IUPCs). 8 The IUPCs are obtained according to the method of patent CN202211426097.3, the sealing plug 213 blocks the perfusion hole 212, and the package 2 is shaken to evenly disperse the mesenchymal stem cells in the dispersion chamber 2112.

[0079] In the experimental group of Bama pigs, intubation sheaths were respectively made in the left femoral artery and the right femoral vein to serve as the blood outlet and the blood inlet respectively. Among them, the inflow tube 41 of the cell therapy delivery system was connected to the outlet of the left femoral artery intubation sheath through a pipeline, and the outflow tube 42 was connected to the inlet of the right femoral vein intubation sheath through a blood vessel interface 42. In the model group, there was no intervention after animal modeling.

[0080] 18 hours after animal modeling, the peristaltic pump 51 was turned on in the experimental group. The blood of the Bama pigs in the experimental group entered the cell encapsulation filter element after passing through the membrane oxygenator 5. The bioactive molecules produced by the cells penetrated into the blood through the porous membrane 22, and the blood was transfused back into the body of the Bama pigs in the experimental group, and the above operation was circulated for 6 hours. At the same time, the Bama pigs in the model group were not intervened after animal modeling.

[0081] Please refer to Appendix Figures 8-12 , Blood samples were taken from the central venous catheter of the Bama pigs in the experimental group and the model group, and the changes in the levels of IL-6, serum creatinine, urea, aspartate aminotransferase and alanine aminotransferase were detected by ELISA.

[0082] Comparing the IL-6 levels of the model group and the experimental group, the IL-6 level in the blood of the model group continued to increase within 18 hours and reached the peak of the inflammatory factor level during the process from 18 hours to 24 hours; after treatment with the cell delivery system in the experimental group, especially during the process from 18 hours to 24 hours of interventional treatment, the IL-6 level in the blood decreased, and after the treatment ended at 24 hours, the IL-6 level resumed the upward trend.

[0083] Comparing the serum creatinine levels of the model group and the experimental group, the creatinine level in the blood of the model group began to increase sharply at 12 hours and remained continuously elevated within 24 hours; after treatment with the cell delivery system in the experimental group, the creatinine level decreased, and after the treatment ended, the creatinine level resumed the upward trend.

[0084] Comparing the in vivo urea levels of the model group and the experimental group, the urea level in the blood of the model group continued to increase within 24 hours; after treatment with the cell delivery system in the experimental group, the urea level of the septic pigs decreased, and after the treatment ended, the urea level resumed the upward trend.

[0085] Comparing the aspartate aminotransferase levels of the model group and the experimental group, the aspartate aminotransferase level in the blood of the model group began to increase significantly from 12 hours and continued to increase within 24 hours; after treatment with the cell delivery system in the experimental group, the aspartate aminotransferase level decreased and tended to be stable.

[0086] Compare the alanine aminotransferase levels of the model group and the experimental group. The alanine aminotransferase level in the blood of the model group started from the time of animal modeling and showed an upward trend in the second stage from 18h to 24h. After treatment with the cell delivery system starting from 18h in the experimental group, the upward trend of the alanine aminotransferase level was not obvious and gradually slowed down and decreased.

[0087] At the same time, compare the survival cycles of the Bama pigs in the experimental group and the model group. Among them, the survival cycle of the Bama pigs in the model group was 32.5h, while the survival cycle of the Bama pigs in the experimental group was 55h after treatment with the cell therapy delivery system. Therefore, during the treatment process, the cell therapy delivery system not only has the function of metabolizing and removing toxins from the blood, but also can improve the patient's internal environment and reduce the level of inflammatory factors through beneficial proteins or exosomes secreted by cells, thereby assisting in the treatment of kidney organ inflammation or functional attenuation-related diseases caused during sepsis.

[0088] In the present invention, unless otherwise clearly specified and defined, terms such as "installation", "connection", "connection", "fixation" and other terms should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or integrated; it can be a mechanical connection or an electrical connection; it can be directly connected, or indirectly connected through an intermediate medium. It can be the communication inside two components or the interaction relationship between two components. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific situations.

[0089] In the description of the present invention, it should be noted that the orientation or positional relationship indicated by terms such as "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings, or the orientation or positional relationship in which the product of the present invention is usually placed during use. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the system or component referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation of the present invention. In addition, terms such as "first", "second", "third", etc. are only used for distinguishing descriptions and cannot be understood as indicating or implying relative importance.

[0090] In addition, terms such as "horizontal", "vertical", "hanging" and other terms do not mean that the components are required to be absolutely horizontal or hanging, but can be slightly inclined. For example, "horizontal" only means that its direction is more horizontal relative to "vertical", and does not mean that the structure must be completely horizontal, but can be slightly inclined.

[0091] In the present utility model, unless otherwise clearly specified or limited, the first feature being above or below the second feature may include the first and second features being in direct contact, or may include the first and second features not being in direct contact but being in contact through additional features therebetween. Moreover, the first feature being above, over, and on the second feature includes the first feature being directly above and obliquely above the second feature, or merely indicating that the horizontal height of the first feature is higher than that of the second feature. The first feature being below, under, and beneath the second feature includes the first feature being directly below and obliquely below the second feature, or merely indicating that the horizontal height of the first feature is lower than that of the second feature.

[0092] Although the description of the present utility model is made in conjunction with the above specific embodiments, it is obvious that those skilled in the art can make many substitutions, modifications, and variations based on the above content. Therefore, all such substitutions, improvements, and variations are included within the spirit and scope of the appended claims.

Claims

1. A cell encapsulation filter element, characterized in that include A collecting container (1) is provided with an inflow joint (121) for allowing liquid to flow into the collecting container (1), and an outflow joint (111) for allowing liquid to flow out of the collecting container (1); as well as The packaging member (2) is arranged in the collection container (1) and is detachably connected to the collection container (1). The packaging member (2) includes a support membrane plate (21), the support membrane plate (21) is provided with a retention cavity (211) for cell retention, and the support membrane plate (21) is provided with a porous membrane (22) for encapsulating the retention cavity (211) and allowing cell products to pass through. The porous membrane (22) covers the surface of the support membrane plate (21) and can be in contact with liquid.

2. The cell encapsulation filter element according to claim 1, wherein The support membrane plate (21) is provided with branches (2111) on the inner wall of the retention cavity (211) for dispersing cells in the retention cavity (211).

3. The cell encapsulation filter element according to claim 2, wherein There are a plurality of branches (2111), and the branches (2111) are distributed at intervals along the inner wall of the retention chamber (211), wherein two branches (2111) arranged opposite to each other are staggered.

4. The cell encapsulation filter element according to claim 2, characterized in that, The branches (2111) extend into the retention chamber (211) and bend in a direction opposite to the direction of gravity, forming a plurality of dispersion chambers (2112) separated by the branches (2111).

5. The cell encapsulation filter element according to claim 1, wherein The support membrane plate (21) is provided with a perfusion hole (212) for perfusing cells into the retention cavity (211), and the support membrane plate (21) is provided with a sealing plug (213) at the perfusion hole (212).

6. The cell encapsulation filter element according to any one of claims 1-5, characterized in that A slot box (3) adapted to the inner wall of the collecting container (1) is provided in the collecting container (1); a fixing hole (31) is provided on the slot box (3); the packaging component (2) is placed in the slot box (3) through the fixing hole (31); the collecting container (1) comprises a shell (12); and a flow hole (32) communicating with the shell (12) is provided on the slot box (3).

7. The cell encapsulation filter element according to claim 6, characterized in that, A plurality of the fixing holes (31) are provided, and the plurality of the fixing holes (31) are arranged at intervals.

8. The cell encapsulation filter element according to claim 1, wherein The outflow joint (111) is arranged on the top of the collecting container (1).

9. A cell therapy delivery system, characterized in that, The invention comprises the cell encapsulation filter element according to any one of claims 1 to 8.

10. The cell therapy delivery system according to claim 9, wherein, It also includes a membrane oxygenator (5) and a liquid delivery device (51) for driving liquid flow, wherein the liquid delivery device (51) is connected to the cell encapsulation filter element to drive liquid flow, and the membrane oxygenator (5) is connected to the inflow connector (121).

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